HDL biology
CETP has dedicated binding sites for cholesteryl ester, triglyceride, and phospholipid that let it ferry lipids between particles (J Biol Chem 1988)
Original title: Plasma cholesteryl ester transfer protein has binding sites for neutral lipids and phospholipids
To investigate the mechanism of CETP-facilitated lipid transfer, purified CETP was incubated with unilamellar egg phosphatidylcholine vesicles containing small amounts of radiolabeled cholesteryl ester or triglyceride, then analyzed by gel filtration chromatography, followed by incubation of the lipid-loaded CETP with LDL. CETP rapidly acquired radiolabeled cholesteryl ester or triglyceride and phosphatidylcholine from the vesicles, then transferred these lipids onward to LDL, binding up to 0.9 mole of cholesteryl ester or 0.2 mole of triglyceride and 11 moles of phosphatidylcholine per mole of CETP. Para-chloromercuriphenylsulfonate, a known inhibitor of cholesteryl ester and triglyceride transfer, reduced the binding of these lipids by CETP. Depending on conditions, CETP eluted either as a lipid-bound monomer or in complexes with vesicles, with the distribution shaped by apoA-I or albumin presence, incubation time, vesicle to CETP ratio, and buffer pH and ionic strength. The authors conclude CETP possesses distinct binding sites for cholesteryl ester, triglyceride, and phosphatidylcholine that equilibrate with lipoprotein lipids, supporting a carrier mechanism for CETP-mediated lipid transfer.
Original abstract
The plasma cholesteryl ester-transfer protein (CETP, Mr 74,000) promotes exchange of both neutral lipids and phospholipids (phosphatidylcholine, PC) between lipoproteins. To investigate the mechanism of facilitated lipid transfer, CETP was incubated with unilamellar egg PC vesicles containing small amounts of cholesteryl ester (CE) or triglyceride, and then analyzed by gel filtration chromatography. There was rapid transfer of radiolabeled CE or triglyceride and PC from vesicles to CETP. The CETP with bound lipids was isolated and incubated with low density lipoproteins (LDL), resulting in transfer of the lipids to LDL. The CETP bound up to 0.9 mol of CE or 0.2 mol of triglyceride and 11 mol of PC/mol of CETP. para-Chloromercuriphenylsulfonate, an inhibitor of CE and triglyceride transfer, was found to decrease the binding of radiolabeled CE and triglyceride by CETP. Under various conditions the CETP eluted either as an apparent monomer with bound lipid (Mr 75,000-93,000), or in complexes with vesicles. The distribution of CETP between these two states was influenced by the presence of apoA-I or albumin, incubation time, vesicle/CETP ratio, and buffer pH and ionic strength. The results indicate that the CETP has binding sites for CE, triglyceride, and PC which readily equilibrate with lipoprotein lipids and suggest that CETP can act as a carrier of lipid between lipoproteins.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.